Taltirelin, a central nervous system activating agent, has two crystal forms (alpha- and beta -forms). Previously it has been reported that methanol (MeOH) as a co-solvent promoted the solvent-mediated phase transformation from alpha -form to beta -form. In the present study, the mechanism of the promotion was investigated. Of the three processes in the solvent-mediated transformation, namely dissolution of the metastable form, nucleation of the stable form, crystal growth of the stable form, MeOH promoted the latter two processes; In particular, the nucleation was strongly promoted. The nOe (nuclear Overhanser effect) data suggested that MeOH promotes the conformational change from the alpha -form to the beta -form. The solute-MeOH interaction resulted in the formation of pseudo-polymorphs of the beta -form (4H(2)O MeOH or H2O . 2MeOH solvate), although these pseudo-polymorphs were exchangeable to the p-form (4H(2)O solvate) under a humid atmosphere. Based on these findings, a possible mechanism of the transformation of taltirelin polymorphs in the presence of MeOH was discussed. (C) 2001 Elsevier Science B.V. All rights reserved.